Reviewed, UniProtKB/Swiss-Prot P37058 (DHB3_HUMAN)

Names and origin

Protein names

Recommended name:
    Testosterone 17-beta-dehydrogenase 3
    EC=1.1.1.64
Alternative name(s):
    Testicular 17-beta-hydroxysteroid dehydrogenase
    17-beta-HSD 3

Gene names

Name:	HSD17B3
Synonyms:	EDH17B3

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	310 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Favors the reduction of androstenedione to testosterone. Uses NADPH while the two other EDH17B enzymes use NADH.
Catalytic activity	Testosterone + NADP(+) = androst-4-ene-3,17-dione + NADPH.
Pathway	Hormone biosynthesis; testosterone biosynthesis.
Tissue specificity	Testis.
Involvement in disease	Defects in HSD17B3 are the cause of male pseudohermaphrodism with gynecomastia (MPH) [MIM:264300]. These individuals have unambiguous female external genitalia at birth, but fail to menstruate at the time of expected puberty and instead virilize as evidenced by growth of the phallus. Breast development may or may not take place.
Sequence similarities	Belongs to the short-chain dehydrogenases/reductases (SDR) family. 17-beta-HSD 3 subfamily.

Ontologies

Keywords
Biological process	Lipid synthesis Steroid biosynthesis
Coding sequence diversity	Polymorphism
Disease	Disease mutation Pseudohermaphroditism
Ligand	NADP
Molecular function	Oxidoreductase
Gene Ontology (GO)
Biological process	male genitalia development Ref.1 Traceable author statement. Source: ProtInc oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW sex determination Inferred from electronic annotation. Source: UniProtKB-KW steroid biosynthetic process Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	microsome Ref.1 Traceable author statement. Source: ProtInc
Molecular function	binding Inferred from electronic annotation. Source: InterPro testosterone 17-beta-dehydrogenase (NADP+) activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 310	310	Testosterone 17-beta-dehydrogenase 3		PRO_0000054573
Regions
	Nucleotide binding	48 – 77	30	NADP By similarity
Sites
	Active site	198	1	Proton acceptor By similarity
	Binding site	185	1	Substrate By similarity
Natural variations
	Natural variant	31	1	V → I: dbSNP rs2066480.		VAR_014870
	Natural variant	56	1	A → T in MPH; Cambridge-2. Affects NADPH cofactor binding.		VAR_016067
	Natural variant	65	1	S → L in MPH.		VAR_016068
	Natural variant	80	1	R → Q in MPH; Gaza.		VAR_006953
	Natural variant	80	1	R → W in MPH.		VAR_006954
	Natural variant	130	1	N → S in MPH; Cambridge-1. Complete loss of activity.		VAR_016069
	Natural variant	176	1	Q → P in MPH.		VAR_016070
	Natural variant	203	1	A → V in MPH.		VAR_006955
	Natural variant	205	1	V → E in MPH.		VAR_016071
	Natural variant	208	1	F → I in MPH.		VAR_016072
	Natural variant	215	1	E → D in MPH.		VAR_016203
	Natural variant	232	1	S → L in MPH.		VAR_006956
	Natural variant	235	1	M → V in MPH.		VAR_006957
	Natural variant	268	1	C → Y in MPH; complete loss of activity.		VAR_016073
	Natural variant	282	1	P → L in MPH.		VAR_016074
	Natural variant	289	1	G → S: dbSNP rs2066479.		VAR_014871

Sequences

	Sequence		Length	Mass (Da)
	P37058-1 [UniParc]. Last modified November 1, 1995. Version 2. Checksum: 0643FF35ED979185	FASTA	310	34,516
	10 20 30 40 50 60 MGDVLEQFFI LTGLLVCLAC LAKCVRFSRC VLLNYWKVLP KSFLRSMGQW AVITGAGDGI 70 80 90 100 110 120 GKAYSFELAK RGLNVVLISR TLEKLEAIAT EIERTTGRSV KIIQADFTKD DIYEHIKEKL 130 140 150 160 170 180 AGLEIGILVN NVGMLPNLLP SHFLNAPDEI QSLIHCNITS VVKMTQLILK HMESRQKGLI 190 200 210 220 230 240 LNISSGIALF PWPLYSMYSA SKAFVCAFSK ALQEEYKAKE VIIQVLTPYA VSTAMTKYLN 250 260 270 280 290 300 TNVITKTADE FVKESLNYVT IGGETCGCLA HEILAGFLSL IPAWAFYSGA FQRLLLTHYV 310 AYLKLNTKVR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Male pseudohermaphroditism caused by mutations of testicular 17 beta-hydroxysteroid dehydrogenase 3." Geissler W.M., Davis D.L., Wu L., Bradshaw K.D., Patel S., Mendonca B.B., Elliston K.O., Wilson J.D., Russell D.W., Andersson S. Nat. Genet. 7:34-39(1994) [PubMed: 8075637] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS MPH GLN-80; VAL-203; LEU-232 AND VAL-235. Tissue: Testis.
[2]	"NIEHS-SNPs, environmental genome project, NIEHS ES15478, Department of Genome Sciences, Seattle, WA (URL: http://egp.gs.washington.edu)." Rieder M.J., Livingston R.J., Daniels M.R., Chung M.-W., Miyamoto K.E., Nguyen C.P., Nguyen D.A., Poel C.L., Robertson P.D., Schackwitz W.S., Sherwood J.K., Witrak L.A., Nickerson D.A. Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS ILE-31 AND SER-289.
[3]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[4]	"Molecular genetics and pathophysiology of 17 beta-hydroxysteroid dehydrogenase 3 deficiency." Andersson S., Geissler W.M., Wu L., Davis D.L., Grumbach M.M., New M.I., Schwarz H.P., Blethen S.L., Mendonca B.B., Bloise W., Witchel S.F., Cutler G.B. Jr., Griffin J.E., Wilson J.D., Russel D.W. J. Clin. Endocrinol. Metab. 81:130-136(1996) [PubMed: 8550739] [Abstract] Cited for: VARIANTS MPH LEU-65; PRO-176; GLU-205; ILE-208; ASP-215 AND LEU-282.
[5]	"A novel missense (R80W) mutation in 17-beta-hydroxysteroid dehydrogenase type 3 gene associated with male pseudohermaphroditism." Bilbao J.R., Loridan L., Audi L., Gonzalo E., Castano L. Eur. J. Endocrinol. 139:330-333(1998) [PubMed: 9758445] [Abstract] Cited for: VARIANT MPH TRP-80.
[6]	"Deleterious missense mutations and silent polymorphism in the human 17beta-hydroxysteroid dehydrogenase 3 gene (HSD17B3)." Moghrabi N., Hughes I.A., Dunaif A., Andersson S. J. Clin. Endocrinol. Metab. 83:2855-2860(1998) [PubMed: 9709959] [Abstract] Cited for: VARIANTS MPH THR-56 AND SER-130, VARIANT SER-289.
[7]	"Substitution mutation C268Y causes 17 beta-hydroxysteroid dehydrogenase 3 deficiency." Lindqvist A., Hughes I.A., Andersson S. J. Clin. Endocrinol. Metab. 86:921-923(2001) [PubMed: 11158067] [Abstract] Cited for: VARIANT MPH TYR-268.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBLGenBankDDBJ	U05659 mRNA. Translation: AAC50066.1. AY341031 Genomic DNA. Translation: AAP88937.1. BC034281 mRNA. Translation: AAH34281.1.
PIR	S43928.
RefSeq	NP_000188.1.
UniGene	Hs.477
3D structure databases
ModBase	Search...
Polymorphism databases
NIEHS-SNPs	Search...
Genome annotation databases
Ensembl	ENSG00000130948. Homo sapiens. [Contig view]
GeneID	3293.
KEGG	hsa:3293.
Organism-specific databases
H-InvDB	HIX0008203.
HGNC	HGNC:5212. HSD17B3.
HPA	HPA015307.
MIM	264300. phenotype. 605573. gene.
Orphanet	752. 46,XY disorders of sex development due to 17-beta-hydroxysteroid dehydrogenase 3 deficiency.
PharmGKB	PA29480.
GenAtlas	Search...
GeneCards	Search...
Phylogenomic databases
HOGENOM	P37058.
HOVERGEN	P37058.
Enzyme and pathway databases
Reactome	REACT_602. Lipid and lipoprotein metabolism.
Gene expression databases
ArrayExpress	P37058.
CleanEx	HS_HSD17B3.
GermOnline	ENSG00000130948. Homo sapiens.
Family and domain databases
InterPro	IPR002198. DHase_sc/Rdtase_SDR. IPR002347. Glc/ribitol_DHase. IPR016040. NAD(P)-bd. [Graphical view]
Gene3D	G3DSA:3.40.50.720. NAD(P)-bd. 1 hit.
PANTHER	PTHR19410. ADH_short_C2. 1 hit.
Pfam	PF00106. adh_short. 1 hit. [Graphical view]
PRINTS	PR00081. GDHRDH. PR00080. SDRFAMILY.
PROSITE	PS00061. ADH_SHORT. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
DrugBank	DB00157. NADH.
NextBio	13063.
SOURCE	Search...

Entry information

Entry name

DHB3_HUMAN

Accession

Primary (citable) accession number: P37058

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 1, 1994
Last sequence update:	November 1, 1995
Last modified:	November 25, 2008
This is version 84 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)